Present studies of carnitine biogenesis indicate the following pathway: Lysine A yields epsilon-N-monomethyllysine B yeilds epsilon-N- dimethyllysine C yields epsilon-N-trimethyllysine D yields gamma- butyrobetaine E yields carnitine. Using contemporary techniques of enzyme purification, an SAM:lysine methyltransferase which appears to catalyze reactions A,B, and C will be isolated from Neurospora. Physical and kinetic studies of the enzyme should confirm or modify present views suggesting the methylase system is a single allosteric enzyme with multiple subunits subject to diverse regulation. A rat kidney slice system will be exploited to establish the chemical nature of overall reaction D which may proceed via alpha or (or beta)-epsilon- N-trimethylaminocaproate. Various metabolic devices will be employed to accumulate hypothetical intermediates, e.g. time course studies, inhibition of postulated reactions by antimetabolites, trapping of intermediates, isotope dilution and incorporation experiments, etc. Rats consuming wheat gluten or rice diets limiting in lysine develop fatty livers and have reduced levels of carnitine in heart and skeletal muscle. Oxidation of (1-C14)-palmitate by heart muscle preparations from such animals will be studied. Reduction in oxidation is anticipated since carnitine is mandatory for the intramitochondrial transport of fatty acids prior to beta-oxidation. The fatty liver observations will be investigated in depth and may bear a relation to that seen in kwashiorkor. Selected plant and animal protein foods consumed where protein calorie malnutrition predominate will be assayed for lysine, methionine, and carnitine. Serum and urinary carnitine will be measured in normal and protein deficient Thai populations. Such studies may establish a lysine:carnitine-precursor:product relationship in man.